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Sophie Camilleri-Broët



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    P1.09 - Pathology (Not CME Accredited Session) (ID 941)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.09-08 - Integrating NGS Information for Staging Multiple Lung Adenocarcinoma: A McGill University Health Centre Retrospective Study. (ID 12635)

      16:45 - 18:00  |  Author(s): Sophie Camilleri-Broët

      • Abstract
      • Slides

      Background

      The incidence of patients with multiple primary lung adenocarcinoma (MPLC) is increasing and the optimal management of these patients remains unclear. Distinguishing between MPLC and intrapulmonary metastases is at the heart of the diagnostic dilemma. The Comprehensive Histologic Assessment (CHA) relies on microscopic examination including histological subtypes, cytological and stromal features. CHA has shown a good reproducibility but with a non-negligible rate of disagreement, even between expert pathologists. Moreover, predictive biomarker testing has become standard of care for lung cancer patients and the use of Next-Generation Sequencing (NGS) is now widely available. The goal of this study was to evaluate how the NGS information may be integrated in the diagnostic strategy for distinguishing between MPLC and patients with stage III/IV disease.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted a retrospective study of all surgical patients with > 1 synchronous lung carcinoma over two years. We identified 59 cases and reviewed initial clinical, pathological and molecular reports. Patients having multifocal lung adenocarcinoma with prominent lepidic component or an adenocarcinoma associated with another histological type were considered as synchronous primaries and not tested for molecular aberrations. The NGS panel analysis using an Illumina miSeq platform included the following genes: AKT1, BRAF, EGFR, ERBB2, FOXL2, GNA11, GNAQ, KIT, KRAS, MET, NRAS, PDGFRA, PIK3A, RET, and TP53.

      4c3880bb027f159e801041b1021e88e8 Result

      Histologically, the majority were considered as MPLC with only four suspected metastases. Twenty-five patients had adenocarcinoma with prominent lepidic component and one case had two different histological differentiations (adenocarcinoma and squamous cell carcinoma). Most of the suspected synchronous primary tumours had different mutations in the separate tumours. Relevant mutations were found in KRAS and P53 genes, with fewer mutations in EGFR, PIK3CA and BRAF genes, in accordance with known frequencies. In 12% of the cases, the NGS was not informative with no molecular mutation in either tumours. One case was reclassified from MPLC to intra-pulmonary metastases and restaged after NGS. For one patient, a TP53 mutation allowed us to reclassify two nodules as metastases from a previous adenocarcinoma originally diagnosed in 2012. In one patient having three separate nodules, different KRAS and TP53 mutations allowed the diagnosis of two nodules as intrapulmonary metastases and one contralateral nodule as synchronous primary adenocarcinoma.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Although CHA is an efficient method for diagnosing MPLC from intra-pulmonary metastases there are still difficult cases with a risk of misdiagnosis. Integrating NGS analysis in the diagnostic strategy may lead to improved quality and accuracy in the staging of MPLC.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.06-33 - Heterogeneity in Care Pathways for Patients with Malignant Pleural Mesothelioma Presenting at a Quaternary Thoracic Oncology Center in Quebec (ID 14346)

      16:45 - 18:00  |  Author(s): Sophie Camilleri-Broët

      • Abstract
      • Slides

      Background

      Malignant pleural mesothelioma (MPM) is a rare disease for which diagnostic and therapeutic trajectories are ill-defined. We hypothesize that MPM patients experience delays during their diagnostic and therapeutic trajectory with significant heterogeneity in care pathways. Thus, we evaluated management practices at the MUHC over the past 10 years to address the need for a centralized program and dedicated care team.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted a retrospective chart review of MPM cases diagnosed at our center from 2006 to 2016. Clinical, pathologic, and treatment variables were collected. We assessed time from first abnormal imaging to definitive diagnosis, time from definitive diagnosis to first treatment and time from definitive diagnosis to palliative care consult. Overall survival was analyzed by Kaplan Meir method.

      4c3880bb027f159e801041b1021e88e8 Result

      We identified 145 patients over a 10-year period and report outcomes on 92 cases with complete data. Demographic data are presented in Table 1. Overall survival was 1.4% at 5-years for all patients, with a median survival of 1 year following a definitive diagnosis. Forty-five percent of patients underwent an investigational PET/CT scan, 89% of patients had M0 status prior to treatment, of whom 20% developed extra-thoracic metastases. Sixty-three percent of patients received some form of treatment. Eight treatment combinations were identified, irrespective of intent, lymph node involvement, and metastatic status. With regards to delays in care pathway, median time from first abnormal imaging to definitive diagnosis was 34 days (IQR 20.5 to 55), definitive diagnosis to first therapeutic intervention was65 days (IQR 35.8 to 163.8), and definitive diagnosis to palliative consult was 289 days (IQR 3 to 1651).

      Table 1. Demographics and treatment characteristics of patients diagnosed with MPM at the McGill University Health Center over a 10-year period.
      Characteristics Overall
      Sample size 92
      Age Number (%)
      Median (IQR) 72 (62-79.5)
      Female Gender, n (%) 19 (20.7)
      Previous or current smoker, n (%) 36 (39.1)
      Asbestos Exposure
      No 20 (21.7)
      Yes 36 (39.1)
      Unknown 36 (39.1)
      Type of MPM
      Biphasic 9 (9.8)
      Desmoplastic 3 (3.3)
      Epitheliod 67 (72.8)
      Sarcomatoid 3 (3.3)
      Not otherwise specified 10 (10.9)
      Treatment
      No 28 (30.4)
      Yes 58 (63.0)
      Unknown 6 (6.5)
      Treatment Course
      Chemotherapy only 8 (13.8)
      Chemo & Radiotherapy 5 (8.6)
      Radiotherapy only 15 (25.9)
      Surgery only 10 (17.2)
      Trimodality therapy 7 (12.1)
      Surgery and Chemo 7 (12.1)
      Surgery and Radiotherapy 4 (6.9)
      Concurrent therapy 2 (3.4)
      Intent at first treatment
      Curative 31 (53.4)
      Palliative 24 (41.4)
      Unknown 3 (5.2)

      8eea62084ca7e541d918e823422bd82e Conclusion

      Overall outcomes for MPM patients presenting at our center are equivalent to historical controls. However, significant heterogeneity and delays exist during the patient trajectory. A centralized approach to diagnosis and treatment may lead to a more efficient and beneficial trajectory for these patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.09 - Pathology (Not CME Accredited Session) (ID 958)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P2.09-07 - Does Metastatic Site Matter for PD-L1 Testing in Stage IV NSCLC? (ID 13385)

      16:45 - 18:00  |  Author(s): Sophie Camilleri-Broët

      • Abstract
      • Slides

      Background

      Stage IV non-small cell lung cancer (NSCLC) often presents with metastasis to multiple distant sites. Currently PD-L1 expression by immunohistochemistry (IHC) testing with Tumor Proportion Score (TPS) ≥ 50% and ≥1% is required for first- and second-line Pembrolizumab treatment respectively. However, it is not well known if PD-L1 expression differs in NSCLC specimens sampled from different distant metastatic sites. In this study, we evaluate PD-L1 expression in distant metastatic sites.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A total of 400 NSCLC specimens from distant metastatic sites are included in this study. The metastatic sites include brain, bone, non-regional lymph nodes, serous membranes (pleura, pericardium and peritoneum) and organs outside the chest (liver, adrenal gland, skin, soft tissue). The samples are either cytology cell blocks, small biopsies or surgical resections. IHC was performed using Dako PD-L1 IHC 22C3 pharmDx. A total of 100 viable tumor cells is required for adequacy. TPS≥ 50% and 1-49% are defined as high and low PD-L1 expression respectively.

      4c3880bb027f159e801041b1021e88e8 Result

      Overall, the rate of TPS >50% ranges from 36-47% in different metastatic organ sites (Table 1). The prevalence of PD-L1 high and low expression is similar for all distant metastatic sites (P=0.91). Brain metastases have a slightly lower rate of high PD-L1 expression but the difference is not statistically significant.

      Table 1. PD-L1 expression in different metastatic sites

      Metastatic sites

      Tumor Proportion Score (TPS)

      Total

       

      ≥50%

      n (%)

      1-49%

      n (%)

      0%

      n (%)

      n (%)

      Brain

      13(36%)

      9 (25%)

      14(39%)

      36 (100%)

      Bone

      21(44%)

      11(23%)

      16(33%)

      48 (100%)

      Nonregional lymph nodes

      6(40%)

      3(20%)

      6 (40%)

      15 (100%)

      Serous membranes

      91(40%)

      62(27%)

      74(33%)

      227 (100%)

      Organ outside chest

      35(47%)

      20(27%)

      19(26%)

      74 (100%)

      Total

      166(42%)

      105(26%)

      129(32%)

      400 (100%)

      P=0.91

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results suggest that the specimens for PD-L1 IHC testing can be sampled from any accessible distant metastatic site.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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